Differential involvement of striato- and cerebello-thalamo-cortical pathways in tremor- and akinetic/rigid-predominant Parkinson's disease

Abstract

Parkinson's disease (PD) presents clinically with varying degrees of resting tremor, rigidity, and bradykinesia. For decades, striatal-thalamo-cortical (STC) dysfunction has been implied in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure:The authors have reported no conflicts of interest. Specific Contributions of AuthorsMechelle M. Lewis: Data acquisition, analysis, and interpretation; obtaining funding for the study, administrative support for the study; primary drafting and critical revision of the manuscript. Guangwei Du: Data analysis and interpretation, drafting and critical revision of the manuscript, Suman Sen: Data acquisition, critical revision of the manuscript. Atsushi Kawaguchi: Statistical analysis of the data and data interpretation. Young Truong: Statistical analysis of the data, data interpretation, critical revision of the manuscript. Seonjoo Lee: Statistical analysis of the data and critical revision of the manuscript. Richard Mailman: Data interpretation and critical revision of the manuscript. Xuemei Huang: Conception and design of the study; data acquisition, analysis, and interpretation; drafting and critical revision of the manuscript; obtaining funding for the study; administration and supervision of the project. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2012 March 17. Zetusky et al., 1985), is less reliably responsive to dopaminergic modulation (Marjama-Lyons and Koller, 2000), and does not worsen at the same rate as bradykinesia and rigidity (Zetusky et al., 1985;Louis et al., 1999;Jankovic and Kapadia, 2001). Recent PD imaging studies suggest dopamine transporter levels and myocardial sympathetic degeneration correlate with hypokinesia/rigidity but not tremor (Spiegel et al., 2007). Finally, there is no correlation between rest tremor and striatal 18 Ffluorodopa uptake in PD patients (Vingerhoets et al., 1997).The pathological hallmark of PD is dopamine neuron loss in the substantia nigra pars compacta (SNc) of the basal ganglia (BG). For decades, a classic model emphasized the role of the BG in modulating cortical function through striatal-thalamo-cortical (STC) circuits (DeLong et al., 1984;Alexander et al., 1986;Albin et al., 1989), the dysfunction of which may lead to bradykinesia and rigidity. This model does not, however, explain PD resting tremor. Emerging evidence suggests the necessity of incorpating cerebello-thalamo-cortical (CTC) circuitry into discussions of motor function in both normal (Kelly et al., 2009) and dysfunctional (Deiber et al., 1993;Neychev et al., 2008;A...

Disrupted Brain Network Hubs in Subtype-Specific Parkinson's Disease

“…To some extent, this circuit is a compensatory mechanism for dopamine deficiency in BG [12,42] and several task-related fMRI studies have further verified hyperactivity in the cerebellum in TD patients. A fludeoxyglucose-PET study identified a PD-tremor related pattern characterized by covarying increases in metabolic features in the dentate nucleus and primary motor cortex [43].…”

“…Furthermore, major reductions in long-range connection in PD patients with mild, or no, cognitive impairment were detected [11]. However, different PD subtypes have different pathophysiological mechanisms and altered functional network patterns [12]. While a pathological interaction between the BG and the cerebellothalamic circuit (cerebello-thalamo-cortex [CTC] pathway) may play an important role in the genesis of resting tremor [13], gait disturbance in PD may in part be associated with the dysfunction of the prefrontal-subthalamic-pedunculopontine loop [14].…”

Early Diagnosis of Alzheimer's Disease and Parkinson's Disease Associated with Dementia Using Cerebral Perfusion SPECT

“…This cerebellar hypoperfusion may be due to the involvement of cerebello-thalamo-cortical circuits, particularly those originating or terminating in the vermis/paravermis region of the cerebellum, which are affected by PD. The cerebellum is an important component in motor control and is known to influence cerebral-cortical activity via cerebello-thalamo-cortical circuits [25,26]. These cerebello-thalamo-cortical circuits have been implicated in somatosensory integration and information updating [26,27].…”

Decreased Dopamine Transporter Binding Ipsilateral to the Clinically More Affected Side in Parkinson's disease: Which Side to Take?

“…Researchers suggest that both the ipsilateral and the contralateral basal ganglia may be associated with abnormal signaling to the cerebellothalamo-cortical circuit, which has been previously shown to be involved in the pathogenesis of several types of tremor, including rest tremor [11,17,18]. Furthermore, the presence of crossed dopaminergic fibers from the basal ganglia to the thalamus has been documented [19,20] in addition to a direct connection between the basal ganglia to both the ipsilateral and the contralateral cerebellum [21].…”